Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is one of the methods to increase the MRI sensitivities by exploiting CEST effects, where the signals of water protons change due to the exchange between exchangeable protons and water protons. The CEST effects are sensitive to exchange rates, which are often pH-dependent. As such, a CEST MRI can be used to noninvasively image pH.
There are many CEST contrast agents that can be used for pH imaging. Some have more than one exchangeable sites (e.g., iopamidol, iopromide); some have a single exchangeable site (e.g., iobitridol, iohexol, and creatine). Composite amide and amine protons from endogeneous composite proteins or peptides can also be used for pH imaging.
Indeed, pH MRI has been applied to investigate pH changes in disorders such as acute stroke and renal injury. However, in addition to being pH dependent, the CEST effect also varies with CEST agent concentration, relaxation rates, and experimental conditions, all of which limit the pH specificity of CEST imaging. For example, quantification of exchange rate with saturation power (QUESP), time (QUEST), and time with ratiometric analysis (QUESTRA) are sensitive to labile proton ratio-weighted exchange rate, their specificity may be limited without knowledge of CEST agent concentration.
One way to decrease the effects of concentration in CEST imaging is through ratiometric CEST imaging by analyzing the relative CEST effects from multiple exchangeable groups. This method substantially simplifies pH determination, but is limited to CEST agents with at least two chemically distinguishable exchangeable sites. Another drawback of this method is that the power level of the saturating radio frequency pulse is not optimal because ratios of CEST measurements from multiple sites using the same B1 field are generated. The optimal B1 level depends on exchange rates, pH, the chemical shift from bulk tissue water, and the difference between chemical shifts of exchangeable sites. As such, the applied B1 may not be optimal for any site, and the precision of measured pH values is compromised.
It would be desirable to have a system and method for pH imaging independent from concentration of the contrast agent, applicable to agents with only one exchangeable site or with multiple exchangeable sites, and with an optimized sensitivity and extended range.